Circulating TGF-β1-related biomarkers in patients with hepatocellular carcinoma and their association with HCC staging scores

TGF-β1 was inversely correlated with E-cadherin but significantly correlated with VEGF. VEGF and AFP had a low coefficient value but statistically significant. A significant correlation was found between E-cadherin and MMP2. In conclusion, TGF-β and E-cadherin are inversely correlated in HCC patients' sera and not related to the BCLC classification nor survival but rather to the biological properties of the tumor.     

Multiple perspectives on mental health outcome: needs for care and service satisfaction assessed by staff, patients and family members

Purpose

Community-based mental health care requires the involvement of staff, patients, and their family members when both planning intervention programmes and evaluating mental health outcomes. The present study aimed to compare the perceptions of these three groups on two important subjective mental health outcome measures—needs for care and service satisfaction—to identify potential areas of discrepancy.

Methods

The sample consisted of patients with a DSM diagnosis of psychosis and attending either outpatient or day centres operating in a community-based care system. Staff, patients and family members were assessed by using the CAN and the VSSS to evaluate, respectively, needs for care and service satisfaction. Kappa statistics were computed to assess agreement in the three groups.

Results

Patients identified significantly fewer basic (e.g. daytime activities, food, accommodation) and functioning needs (e.g. self-care, looking after home, etc.) than staff or family members. Only fair levels of agreement were found in the three groups (average kappa was 0.48 for staff and patients, 0.54 for staff and family members, and 0.45 for patients and relatives), with patients and family members showing more areas of discrepancies in both needs and service satisfaction.

Conclusions

These findings provide further support for the idea that mental health services should routinely involve patients and their relatives when planning and evaluating psychiatric intervention and that this policy is a premise for developing a partnership care model.     

Dorsolateral medullary ischemic infarction causing autonomic dysfunction and headache: a case report

Stroke can present, among other signs, with headache. Here, we describe the case of a man suffering from severe orbitary pain and autonomic dysfunction secondary to dorsolateral medullary ischemia. The anatomical relationship between lesion and symptomatology could be an indirect sign of hypothalamospinal tract involvement in the genesis of autonomic dysfunction and headache resembling a trigeminal autonomic cephalalgia.     

Effect of COMT genotype on aggressive behaviour in a community cohort of schizophrenic patients

Although the etiology of aggression is multifactorial, many studies have associated the Val158Met polymorphism of the COMT with aggression in schizophrenia. This study tests the hypothesis that Met/Met patients display more episodes of aggression and violent behaviour than Val/Val patients in a 6 year follow-up cohort of subjects with schizophrenia in contact with the South-Verona Community-based Mental Health Service. Out of the 141 subjects with an ICD-10 SCAN-confirmed diagnosis of schizophrenia, 115 completed both baseline and follow-up assessments (81.6% of the baseline cohort). Of these, 80 subjects (70%) were genotyped and rated for aggression using the Overt Aggression Scale.     

A 1 Mb de novo deletion within 11q13.1q13.2 in a boy with mild intellectual disability and minor dysmorphic features

We report a 11 year old male patient ascertained for mild intellectual disability and minor dysmorphic features, carrying a 1 Mb de novo deletion on chromosome 11q13.1q13.2 detected by aCGH. This is the first report of a deletion in this region in a patient presenting with intellectual impairment and mild dysmorphic traits. The 1 Mb deleted area encompasses 47 RefSeq genes, including Cornichon homologue 2 (CNIH2), Cofilin-1 (CFL1) and neuronal PAS domain-containing protein 4 (NPAS4), which are highly expressed in the central nervous system. Knockout of the CNIH2 and CFL1 orthologues in animals results in migration disturbances, while low or no expression of Npas4 in mice results in impairment of memory and learning. These three genes have previously been suggested as candidate genes for neurological disorders.     

In vitro anti-mesothelioma activity of cisplatin�Cgemcitabine combinations: evidence for sequence-dependent effects

Purpose

The present study addresses the optimization of gemcitabine?Ccisplatin protocols currently adopted in the clinical management of malignant pleural mesothelioma (MPM), using cell lines derived from different histological subtypes of MPM as an in vitro model.

Methods

MPM cell lines were exposed either to single drugs or to their combinations, using a fixed dose ratio. Possible mechanisms for synergistic interactions were investigated by cell cycle analysis, western blot analysis of p53 phosphorylation status, and neutral comet assay to detect double strand breaks.

Results

Four-hour pre-treatment with gemcitabine followed by 68-h exposure to cisplatin was found to exert synergistic activity in both epithelioid and sarcomatoid MPM subtypes, inducing a strong S-phase arrest that correlated with accumulation of double-strand breaks (DSBs).

Conclusion

The antiproliferative effects of the gemcitabine/cisplatin combination in mesothelioma cells can be maximized by pre-treatment with gemcitabine, suggesting that this drug increases cisplatin-induced DSBs by inhibiting DNA adduct repair.     

Natural killer cells efficiently reject lymphoma silenced for the endoplasmic reticulum aminopeptidase associated with antigen processing

The endoplasmic reticulum aminopeptidase ERAAP is involved in the final trimming of peptides for presentation by MHC class I (MHC-I) molecules. Herein, we show that ERAAP silencing results in MHC-I peptide-loading defects eliciting rejection of the murine T-cell lymphoma RMA in syngeneic mice. Although CD4 and CD8 T cells are also involved, rejection is mainly due to an immediate natural killer (NK) cell response and depends on the MHC-I-peptide repertoire because replacement of endogenous peptides with correctly trimmed, high-affinity peptides is sufficient to restore an NK-protective effect of MHC-I molecules through the Ly49C/I NK inhibitory receptors. At the crossroad between innate and adaptive immunity, ERAAP is therefore unique in its two-tiered ability to control tumor immunogenicity. Because a large fraction of human tumors express high levels of the homologous ERAP1 and/or ERAP2, the present findings highlight a convenient, novel target for cancer immunotherapy.